Reduced Relative Dose Intensity (RDI) in Patients with Aggressive Non-Hodgkin’s Lymphoma (NHL).

Introduction: A nationwide survey of oncology practices has previously demonstrated that half of patients with aggressive NHL receive substantial reductions in RDI potentially compromising response rates and long term outcomes. Further study is needed of those factors associated with treatment-related complications and reduced RDI in this population.

Methods: A nationwide survey of 567 oncology practices was undertaken between June 1999 and December 2001 with data extracted from the records of 1,620 adult patients with aggressive NHL treated with CHOP (N=1,367), CHOP-R (N=117) or CNOP (N=136). Outcomes included febrile neutropenia (FN), reduced RDI and disease response to treatment. Multivariate logistic and proportional hazards regression analyses based on common demographic, treatment and disease variables and prophylactic colony-stimulating factor (CSF) provided adjusted odds ratios and hazards ratios, respectively.

Results: FN was reported in 319 (20%) patients of which 80% were hospitalized. The initial episode occurred within the first two cycles of treatment in 60% of patients with FN. Independent predictors of FN risk included age >60 (1.5), female gender (1.5), ECOG >2 (1.9) and liver disease (2.0) with a reduction in risk with prophylactic CSF (0.77). The risk of FN was significantly reduced with prophylactic CSF in patients >60 years of age (HR=.51 [.29,.88]). The overall RDI was 79% with planned and unplanned reductions of 12% and 9%, respectively. RDI <85% of standard dose intensity occurred in 52% of patients including: age >60 (58%), ECOG >2 (56%), stage ≤2 (58%), cardiovascular disease (60%), liver disease (71%), renal disease (58%) and diabetes (59%). Independent predictors of planned reductions in RDI were older age, stage ≤2, heart disease, liver disease, regimen and poor chemotherapy response with less reduction with the addition of prophylactic CSF (R²=0.40; P<.0001). Independent predictors of unplanned reductions in RDI were younger age, diabetes and stage ≤2 with less reduction with the addition of prophylactic CSF (R²=0.13, P<.001).

Conclusions: This practice-based study confirms previous reports of a high level of planned and unplanned reductions in RDI in patients with aggressive NHL. Factors associated with reduced dose intensity include age, comorbid conditions, regimen, stage and no prophylactic CSF.